Pitfalls in the measurement and interpretation of thyroid function tests  Olympia Koulouri, MRCP, Carla Moran, MRCPI, David Halsall, PhD, FRCPath, Krishna Chatterjee, FRCP, Mark Gurnell, PhD, FRCP  Best Practice & Research Clinical Endocrinology & Metabolism  Volume 27, Issue 6, Pages 745-762 (December 2013) DOI: 10.1016/j.beem.2013.10.003 Copyright © 2013 The Authors Terms and Conditions

Fig. 1 Schematic representation of the hypothalamic–pituitary–thyroid axis and the various factors governing thyroid hormone transport, metabolism and action at the tissue/cellular level. Key: α1, TRα1; β1, TRβ1; β2, TRβ2; CoA, coactivator; DNA, deoxyribonucleic acid; MCT8, monocarboxylate transporter 8; RXR, retinoid X receptor; SA, somatostatin; T3, triiodothyronine; T4, thyroxine; TR, thyroid receptor; TRE, thyroid response element; TRH, thyrotropin releasing hormone; TSH, thyroid stimulating hormone (thyrotropin). Best Practice & Research Clinical Endocrinology & Metabolism 2013 27, 745-762DOI: (10.1016/j.beem.2013.10.003) Copyright © 2013 The Authors Terms and Conditions

Fig. 2 Different patterns of thyroid function tests and their causes. Key: ATDs, antithyroid drugs; FDH, familial dysalbuminaemic hyperthyroxinaemia; FT4, free thyroxine; FT3, free triiodothyronine; NTI, non-thyroidal illness; TKIs, tyrosine kinase inhibitors; TSH, thyroid-stimulating hormone/thyrotropin [*signifies that TSH may be either fully suppressed (for example as seen in classical primary hyperthyroidism) or partially suppressed (i.e. measurable, but below the lower limit of normal)]. Reproduced with permission from: Koulouri O, Gurnell M. How to interpret thyroid function tests. Clin Med 2013; 13:282–6. Copyright © 2013 Royal College of Physicians. Best Practice & Research Clinical Endocrinology & Metabolism 2013 27, 745-762DOI: (10.1016/j.beem.2013.10.003) Copyright © 2013 The Authors Terms and Conditions

Fig. 3 Protocol for supervised thyroxine absorption test, followed by weekly supervised thyroxine administration. Key: ECG, electrocardiogram; FT4, free thyroxine; FT3, free triiodothyronine; TSH, thyrotropin (thyroid stimulating hormone). Best Practice & Research Clinical Endocrinology & Metabolism 2013 27, 745-762DOI: (10.1016/j.beem.2013.10.003) Copyright © 2013 The Authors Terms and Conditions

Fig. 4 Schematic representation of an immunoradiometric assay for measurement of serum TSH. a. TSH is bound by both capture (immobilised) and detection (labelled) antibodies. b. The presence of a human anti-animal (HAA) or heterophilic antibody that is capable of cross-linking the capture and detection antibodies even in the absence of analyte (TSH), results in positive assay interference. c. In contrast, an HAA or heterophilic antibody that binds either the capture or detection antibody to prevent crosslinking (even in the presence of TSH) results in negative assay interference. Best Practice & Research Clinical Endocrinology & Metabolism 2013 27, 745-762DOI: (10.1016/j.beem.2013.10.003) Copyright © 2013 The Authors Terms and Conditions

Fig. 5 Algorithm for the interpretation of discordant TFTs. Key: FT3, free triiodothyronine; FT4, free thyroxine; HPT, hypothalamic–pituitary–thyroid; RR, reference range; TFTs, thyroid function tests; TH, thyroid hormones; L-T4, levothyroxine; NTI, non-thyroidal illness, TT4, total thyroxine; TT3, total triiodothyronine; TSH, thyroid stimulating hormone (thyrotropin); TH, thyroid hormones; TBG, thyroxine binding globulin. Best Practice & Research Clinical Endocrinology & Metabolism 2013 27, 745-762DOI: (10.1016/j.beem.2013.10.003) Copyright © 2013 The Authors Terms and Conditions